Apparatus producing a vacuum in several cavities of a microtitration filter plate, and corresponding method

ABSTRACT

Apparatus producing a vacuum in several cavities configured in a microtitration filter plate, each cavity comprising an upper sample liquid input aperture and a lower aperture fitted with a filter covering the aperture cross-section, said apparatus including a device which produces a vacuum and which can be connected to the lower apertures in such manner that upon connection a vacuum can be applied to the apertures and that during the vacuum stage the sample liquid in the cavities shall be aspirated through the filters, said apparatus being characterized in that a flexible plate can be mounted to make planar contact at the side of the upper cavity apertures on the microtitration filter plate, and in that said plate, when mounted on the microtitration plate and when the vacuum is applied, shall hermetically seal the upper apertures of unfilled cavities.

[0001] The present invention relates to apparatus defined in the preamble of claim 1 and to a method defined in the preamble of claim 9.

[0002] Apparatus and methods of this kind are used in parallel processing of several liquid samples by means of vacuum filtration in microtitration filter plates. Like conventional microtitration plates, microtitration filter plates exhibit also for instance 96 or 384 cavities, but contrary to the case of microtitration plates, the microtitration filter plates comprises a lower cavity aperture fitted with a filter covering this aperture's cross-section.

[0003] Herein the concept of “microtitration filter plates” shall cover not only the conventional formats (96, 384), but any planar test unit comprising several cavities to be used in a similar way.

[0004] When the samples are processed conventionally, they are first pipetted into the cavities of the microtitration filter plates. Then the lower cavities' apertures are subjected to vacuum whereby the sample liquid is aspirated through the filters. As a rule a microtitration plate is mounted underneath the microtitration filter plate and the filtrates from the latter are collected in the former.

[0005] Typically the above described vacuum filtration is carried out using apparatus comprising a chamber allowing vacuum being produced in it. First the microtitration plate serving to collect the sample liquid is inserted into said chamber. Then the microtitration filter plate is mounted in or on the vacuum chamber, appropriate seals between the rim of the microtitration filter plate and the vacuum chamber assuring proper sealing. The typically applied vacuum ranges from 100 to 900 hPa.

[0006] Accordingly, when testing, the upper apertures of the microtitration filter plate are freely accessible outside the apparatus, whereas the lower apertures are subjected to the vacuum produced in the vacuum chamber.

[0007] However a problem may arise when not all microtitration filter plate cavities are filled with sample liquid. These unfilled cavities induce an effect of air leakage that may degrade the applied vacuum.

[0008] In order to avoid this air leakage effect, it is commonplace to tape shut or the like the upper apertures of unfilled cavities before vacuum filtration takes place. Alternatively however, unfilled cavities might be filled for instance with water. While both measures do reduce or even avert the problem of air leakage, on the other hand they are comparatively time-consuming and practically preclude automation.

[0009] Therefore it is the objective of the present invention to create an apparatus and a method allowing carrying out the vacuum filtration of microtitration filter plates or of similar test units comprising several cavities in a simpler manner.

[0010] This goal is attained using apparatus defined by the features of claim 1 and a method defined by the features of claim 9.

[0011] Accordingly the apparatus of the present invention comprises a flexible plate which, at the side of the upper cavity apertures, may be assembled in a way to make planar contact with and on the microtitration filter plate. The properties of the flexible plate are selected in such a way that, following said plate's mounting on the microtitration filter plate and in the presence of applied vacuum, said plate shall be able to hermetically seal the upper apertures of the unfilled cavities.

[0012] In general appropriate flexible plates are designed in a manner that upon application of vacuum, said plates shall be aspirated slightly into the upper apertures of the unfilled cavities and then said plates will rest in sealing manner on the upper apertures' rims.

[0013] The concept of “plate” herein denotes all suitable forms, therefore including also mats, foils etc.

[0014] The term “flexible plate” also includes a basically rigid, planar structure fitted on its side engaging the microtitration filter plate with an appropriate, flexible coating, for instance a silicone mat.

[0015] Preferably the flexible plate shall only close the upper apertures of the unfilled cavities, not the apertures of the filled ones, because the suction at the upper apertures of the latter is considerably lower than at the unfilled ones.

[0016] However the scope of the present invention also covers the case of the flexible plate hermetically covering the filled cavities. In this mode, which applies in particular to microtitration filter plates of large numbers of cavities, the plate need only be lifted off the microtitration filter plate once or several times during vacuum filtration and be lowered again after the cavities have been vented.

[0017] In both modes of implementation, air leakage during vacuum filtration due to the unfilled cavities can be averted in especially simple manner.

[0018] The flexible plate designed in the manner of the invention is required, as already mentioned above, to seal the apertures of unfilled cavities when it makes planar contact with a microtitration filter plate to which a vacuum is applied.

[0019] Flexible plates preferably made of resilient plastic were found especially suitable in this respect. A silicone mat about 1.5 to 3 mm thick and with a shore hardness of 30-40 for instance is particularly appropriate. Other materials however also are applicable. Rubber and the like obviously may also be used besides plastics.

[0020] One substantial advantage offered by the flexible plate of the present invention is the new freedom from having to check, before vacuum filtration begins, whether any unfilled cavities are present in a microtitration filter plate, which, if found, then would have to be taped shut or the like or be separately filled.

[0021] The flexible plate of the present invention is mounted over all cavities of the microtitration filter plate and thereupon, depending on the nature of said plate and the density of the cavities, will hermetically and selectively seal only the unfilled cavities or all upper apertures of the cavities. The latter case does require venting once or several times during the vacuum filtration stage by briefly raising and then lowering again the plate, this operation however amounting to substantial operational simplification over the state of the art.

[0022] Accordingly the invention makes automation possible, that is, the flexible plate of the invention can be lowered onto and subsequently raised again from the microtitration filter plate in suitably controlled manner by means of a displaceable adjustment device or a corresponding gripper tool cooperating with the apparatus. Furthermore, to improve handling, the plate may be received in a support frame or the like.

[0023] In this regard, the control device may be designed in that the flexible plate shall automatically make planar contact with the microtitration filter plate when a vacuum is applied.

[0024] The control device may further be programmed in such a way that during the applied vacuum stage, the plate may be lifted off and then repositioned on the microtitration several times during said vacuum stage.

[0025] Alternatively and just as well, the plate of the invention may be designed to be a manual accessory of the apparatus of this invention.

[0026] The invention not only relates to said apparatus, but also to a corresponding method whereby the above described plate can be moved into planar contact with the upper side for instance of a microtitration filter plate for the purpose of avoiding air leakage during vacuum filtration, and to using such a plate for such purposes.

[0027] As already mentioned above, the prior art only knew—to avoid air leakage—to tape shut or the like the upper apertures of unfilled cavities.

[0028] Relative to that state of the art, the method of the invention offers much simplified implementation. In the invention, merely one flexible plate exhibiting the above described properties need be mounted in such manner on the microtitration filter plate that all cavities shall be covered.

[0029] When thereupon the vacuum conventionally used is applied for vacuum filtration, namely in a range from 100 hPa to 900 hPa, then the flexible plate shall rest in sealing manner on the upper rims of the unfilled cavities due to the suction arising there. The suction in the filled cavities on the other hand shall be substantially lower and as a rule no sealing takes place at latter and enough air may flow into the cavities as the sample liquid is aspirated through the filters.

[0030] If some of the filled cavities are expected to be hermetically sealed, then the plate only need being raised once or several times during vacuum filtration off the microtitration filter plate and venting said cavities shall be carried out in this manner.

[0031] The flexible plate may also be held for instance in a support frame to facilitate handling. However said plate also may be used directly in its formatted form in the method of the invention.

[0032] Lastly the invention also includes using appropriately flexible plates in order to preclude air leakage during vacuum filtration of microtitration filter plates.

[0033] The invention is elucidated below in relation to one FIGURE of an illustrative embodiment.

[0034] This FIGURE is a schematic section of a vacuum producing apparatus 10.

[0035] The apparatus 10 comprises a housing 11 defining a chamber 12 which is connected through a borehole 13 and a corresponding tube 14 to a vacuum generating device 15.

[0036] A removable frame 16 rests on the housing 11. A peripheral sealing ring 17 is configured between the frame 16 and the housing 11.

[0037] A microtitration filter plate 19 is mounted in the frame 16 above a peripheral sealing strip 18 and comprises several cavities 20, 21, 22 and 23 of which cavities 21 and 23 are unfilled and cavities 20, 22 are filled with the sample liquid 25.

[0038] The cavities comprise an upper aperture 25 and a lower aperture 26. A filter 27 is mounted in the zone of the lower aperture and covers said aperture's cross-section, the sample liquid 24 being aspirated through said filter during vacuum filtration.

[0039] In order to collect the sample liquid 24, i.e. its particular filtrates, a microtitration plate 29 is inserted into the vacuum chamber 12 and is held in place by an internal peripheral lip 28, and comprises cavities 30 that are associated with the cavities 20 through 23 of the microtitration plate 19.

[0040] Typically the shown configuration shall be the testing configuration. In that case the device 15 applies a vacuum to the chamber 12 and the liquid 24 shall be aspirated through the filters 27 into the particular associated cavities 30 of the microtitration plate 29.

[0041] Following filtration, the frame 16 together with the microtitration filter plate 19 is removed from the housing 11 whereupon the microtitration plate 29 can be removed from the apparatus 10 for further processing.

[0042] As mentioned above, there is an air leakage problem in conventional apparatus in the region of the unfilled cavities 21, 23 that may interfere with the appropriate vacuum.

[0043] To remedy such a case, the invention provides a flexible plate 32 received in a support frame 31 and displaceable manually or by means of appropriate adjustment devices into planar contact with the upper surface of the microtitration filter plate 19.

[0044] The plate 32 is designed in a manner that when a vacuum acts on the unfilled cavities 21, 23, this plate shall be slightly aspirated into said cavities and in this manner shall seal the upper aperture 25 of these cavities. However the suction effect applied to the zone of the upper aperture 25 of filled cavities 20 and 22 shall be insufficient in the preferred case to entail a hermetic seal. Therefore, in the preferred case, enough air for filtration may flow through these filled cavities.

[0045] In case of doubt, the flexible plate 32 may be raised once or several times off the microtitration filter plate 19, whereby all cavities shall be vented and next filtration may continue even if the plate 32 when making contact with the filled cavities were to seal them. This case may be encountered in particular with formats of large numbers of cavities. Illustratively in 384 microtitration filter plates, one filled cavity may be surrounded by unfilled cavities, the plate then being aspirated so tightly against the surface of the microtitration filter plate that air is precluded from flowing even into the said filled cavity. 

1. Apparatus producing a vacuum in several cavities which are configured in a microtitration filter plate, each cavity comprising one upper aperture receiving sample liquid and one lower aperture fitted with a filter covering the aperture's cross-section, said apparatus including a device to produce a vacuum which can be connected to the lower apertures to apply a vacuum to the cavities, whereupon the sample liquid in these cavities can be aspirated through said filters, characterized in that moreover a flexible plate (32) is affixable in planar contact with and at the side of the upper apertures (25) of the cavities (20, 21, 22, 23) on the microtitration filter plate (19) and is designed to hermetically seal the upper apertures (25) of the unfilled cavities (21, 23) when affixed on the microtitration filter (19) and vacuum is applied.
 2. Apparatus as claimed in claim 1, characterized in that when being mounted on the microtitration filter plate (19) the plate (32) hermetically seals only the upper apertures (25) of the unfilled cavities (21, 23).
 3. Apparatus as claimed in either of claims 1 and 2, characterized in that the plate (32) is made of elastically deforming plastic or of rubber.
 4. Apparatus as claimed in one of claims 1 through 3, characterized in that the plate (32) is a foil or a mat of silicone.
 5. Apparatus as claimed in one of claims 1 through 4, characterized in that the plate (32) is received in a support frame (31) in turn received in the apparatus (10) so as to be displaceable between a lowered position on the microtitration filter plate (19) and a raised position.
 6. Apparatus as claimed in claim 5, characterized in that it comprises a control device which upon application of vacuum shall automatically move the flexible plate (32) into planar contact with the microtitration filter plate (19).
 7. Apparatus as claimed in claim 6, characterized in that the control device at least once raises the plate off the microtitration filter plate and then lowers it again during vacuum application.
 8. Apparatus as claimed in one of claims 1 through 7, characterized in that the flexible plate is designed to be an accessory for the apparatus (10).
 9. A method for producing a vacuum in several cavities configured in a microtitration filter plate, said cavities each exhibiting an upper aperture to be loaded with sample liquid and a lower aperture fitted with a filter covering the aperture cross-section, vacuum being applied simultaneously to several lower apertures to aspirate the sample liquid in the cavities through the filters whereas unfilled cavities are hermetically sealed in the region of their upper apertures, characterized in that a flexible plate (32) is mounted in planar contact in such manner at the side of the upper apertures (25) of the cavities (20, 21, 22, 23) on the microtitration filter plate (19) that filled cavities also shall be covered, the plate (32) being designed so that when it is mounted on the microtitration filter plate (19) and vacuum is applied, it shall hermetically seal the upper apertures (25) of unfilled cavities (21, 23).
 10. Method as claimed in claim 9, characterized in that the plate (32) at least once during the stage of applied vacuum is raised to vent the cavities (20, 21, 22, 23) of the microtitration filter plate (19) and then shall be lowered again.
 11. Method as claimed in either of claims 9 and 10, characterized in that the plate (32) is a mat or foil of silicone.
 12. Using a flexible plate to cover the upper side of microtitration filter plates during vacuum filtration to preclude air leakage due to any unfilled cavities. 